In 2008 it was reported that non-medical use of pain relievers among the population aged 12 or older in the United States was second highest in prevalence among illicit drugs, after marijuana. Abuse of prescription pharmaceutical products follows the increasing availability of opioid dosage forms due to the more aggressive treatment of chronic pain in the populace. The increasing number of abusers, increasing availability, and the destructive/addictive potential of opiates make prescription pharmaceutical abuse a matter of public health concern.
Several routes of administration are commonly attempted by abusers. For example, the pharmaceutical dosage form may be chewed, or it may be crushed or pulverized into a powder and administered intranasally (i.e., snorted). Alternatively, the intact or tampered pharmaceutical dosage form may be dissolved in a suitable solvent and administered parenterally (i.e., injected intravenously), or the intact or tampered dosage form may be smoked.
To deter misuse and/or abuse of pharmaceutical dosage forms with extended drug release, multiple strategies have been employed. First, a chemical approach has been utilized to include an opioid antagonist in opioid pharmaceutical dosage forms. The opioid antagonist, which is not orally active, will substantially block the analgesic effects of the opioid when one attempts to abuse the tampered dosage form via snorting or injecting. Second, aversive agents and/or bitter agents have been added to pharmaceutical formulations to prevent abuse of the active pharmaceutical ingredient. This approach, however, could cause adverse effects in the patient population due to the properties associated with these agents. Third, a safer alternative is to incorporate excipients that provide a physical barrier in which abuse of the API is deterred. In one case, this is accomplished by incorporating the API into a polymeric matrix tablet containing high molecular weight gel forming polymers such as polyethylene oxide. The polymeric matrix tablet has increased hardness and retains a plastic-like nature after curing at a temperature above the softening temperature of the polyethylene oxide. The resultant tablet dosage form is difficult to crush or chew and forms a viscous gel when the dosage form comes into contact with a suitable solvent. However, because polyethylene oxide forms oxidative peroxide radicals when heated, APIs susceptible to oxidative degradation should be incorporated into such dosage forms with care. Alternately, the conditions for curing the dosage form with an API sensitive to oxidation must be tightly controlled, sometimes limiting the tamper resistant properties thereof. Similarly, thermolabile APIs cannot be incorporated into these cured dosage forms.
To impart abuse deterrent properties to pharmaceutical dosage forms comprising polymers, the polymers generally need to be plasticized. Typically, polymers are plasticized by plasticizers using either of two commonly used methods that thoroughly incorporate the plasticizers into the polymers. The most common method is hot melt extrusion. In this process, polymers and plasticizers are intimately mixed under heat and pressure and then extruded out of small orifices. Recent strides in this technique have resulted in acceptable material throughput for large scale manufacturing. A less common method for incorporating a plasticizer into a polymer involves dissolving the polymer and the plasticizer in a suitable co-solvent and then spray drying the mixture. This method has a very low material throughput and also has the significant technical issue of the plasticized polymers sticking to the spray drier. However, in both of these methods, the resultant plasticized polymer mass can be a sticky, non-flowable material that poses additional processing problems in milling, blending, and compressing with conventional manufacturing equipment.
Thus, there is a need for pharmaceutical dosage forms comprised of polymers that provide extended release of the API and are resistant to abuse and/or misuse. Additionally, there is a need for the easy manufacture of a plasticized polymer mass into a dosage form utilizing conventional processing equipment.